J Psychopharmacol

Antidepressant effectiveness may diminish after treatment interruption

September 17, 2025

Study details: This systematic review included 12 studies (N = 594) across psychiatric conditions, examining loss of antidepressant efficacy after treatment interruption and reinitiation. Studies were included regardless of language or publication date.

Results: Non-response rates ranged from 4% to 57%. Many patients who'd previously responded to antidepressants failed to regain efficacy after a drug-free interval, suggesting that intermittent use or cycling may impair future treatment response.

Clinical impact: Interrupting antidepressant therapy may reduce the likelihood of future responsiveness, contributing to persistent depression despite rising prescription rates. Consider discussing these risks with patients, as reinitiation may not reliably restore prior benefit.

Source:

Majkic N, et al. (2025, September 13). J Psychopharmacol. Loss of responsiveness on reinstatement of antidepressants after treatment interruption - A systematic review. https://pubmed.ncbi.nlm.nih.gov/40944456/